Kither Biotech focuses on the treatment of rare pulmonary diseases, including Cystic fibrosis (CF) and Idiopathic Pulmonary Fibrosis (IPF), two very different conditions for which there are very few pharmacological treatments with still an high unmet medical need. Kither has developed two proprietary chemical moieties that modulate signal transduction events controlled by PI3K enzymes.
As kinases, PI3K enzymes amplify extracellular signals inside the cell and control metabolism and proliferation. On these premises, Kither developed a small molecule inhibitor, KIT-CL27, that can block the enzymatic function of all members of the PI3K family. KIT-CL27 was optimised for inhaled treatment and offers a superior safety profile as a prodrug, this means that it is inactive in itself but can penetrate cell membranes and convert into an active compound within cells. The active compound is negatively charged, non-diffusible and rapidly secreted by the kidneys when it is carried in the blood (Campa et al., “Nature Communications” 2018).
This pharmacological profile allows it to restrict the anti-PI3K activity to the first targeted cells, thus drastically reducing the known toxic effects of PI3K inhibition. For example, systemic PI3K inhibitors alter the patient’s blood glucose levels, but KIT-CL27, when administered in the lungs, actively blocks the proliferation of IPF fibroblasts (Campa et al., “Nature Communications” 2018) but has no global effect on blood glucose. In IPF, alterations in PI3K signalling contribute to excessive fibroblast growth, which may limit pulmonary compliance and function. The ability of KIT-CL27 to act locally with limited side effects and systemic effects makes it an ideal molecule for the inhaled therapies used to treat this serious condition as observed in our preclinical studies (Campa et al., “Nature Communications” 2018).